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WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis

K. Kaiser, D. Gyllborg, J. Procházka, A. Salašová, P. Kompaníková, FL. Molina, R. Laguna-Goya, T. Radaszkiewicz, J. Harnoš, M. Procházková, D. Potěšil, RA. Barker, ÁG. Casado, Z. Zdráhal, R. Sedláček, E. Arenas, JC. Villaescusa, V. Bryja,

. 2019 ; 10 (1) : 1498. [pub] 20190402

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19027676

WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.

Central European Institute of Technology 625 00 Brno Czech Republic

Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases Institute of Molecular Genetics of the CAS v v i Prumyslova 595 Vestec 252 42 Czech Republic

Departamento de Anatomía y Radiología Facultad de medicina Universidad de Valladolid Ramón y Cajal 5 47005 Valladolid Spain

Department of Experimental Biology Faculty of Science Masaryk University Brno 62500 Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno 62500 Czech Republic Division of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 171 77 Sweden

Department of Experimental Biology Faculty of Science Masaryk University Brno 62500 Czech Republic Division of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 171 77 Sweden Psychiatric Stem Cell Group Neurogenetics Unit Center for Molecular Medicine Department of Molecular Medicine and Surgery Karolinska University Hospital Stockholm 171 76 Sweden

Division of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 171 77 Sweden

Division of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 171 77 Sweden Danish Research Institute of Translational Neuroscience Department of Biomedicine Aarhus University Aarhus C 8000 Denmark

John van Geest Centre for Brain Repair and Cambridge Stem Cell Institute University of Cambridge Cambridge CB2 0PY UK

Citace poskytuje Crossref.org

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$a WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis / $c K. Kaiser, D. Gyllborg, J. Procházka, A. Salašová, P. Kompaníková, FL. Molina, R. Laguna-Goya, T. Radaszkiewicz, J. Harnoš, M. Procházková, D. Potěšil, RA. Barker, ÁG. Casado, Z. Zdráhal, R. Sedláček, E. Arenas, JC. Villaescusa, V. Bryja,
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$a WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.
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$a Salašová, Alena $u Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden. Danish Research Institute of Translational Neuroscience, Department of Biomedicine, Aarhus University, Aarhus, C 8000, Denmark.
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$a Arenas, Ernest $u Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden. ernest.arenas@ki.se.
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$a Villaescusa, J Carlos $u Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic. carlos.villaescusa@gmail.com. Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden. carlos.villaescusa@gmail.com. Psychiatric Stem Cell Group, Neurogenetics Unit, Center for Molecular Medicine, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, 171 76, Sweden. carlos.villaescusa@gmail.com.
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